1. Field of the Invention
The present invention relates to N-[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester in the crystalline form, which is useful as a sweetener.
2. Description of the Background
In recent years, as eating habits have been improved to a high level, obesity caused by excessive sugar intake and diseases accompanied by obesity have become important health problems. Accordingly, the development of a low-calorie sweetener (sweetening agent) that replaces sugar has been in great demand. As a sweetener that has been widely used at present, there is aspartame which is excellent in safety and quality of sweetness. And, some novel aspartame derivatives are excellent as sweeteners with respect to the degree (potency) of sweetness or the like as compared to aspartame have been found, see WO 99/52937.
Among such aspartame derivatives, N-[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester, which is referred to as xe2x80x9cobject compoundxe2x80x9d or the like herein, is a particularly suitable sweetener. In this respect, in the above described international patent publication WO 99/52937, a process for purifying N-[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester through the step of subjecting a concentrated reaction solution containing the compound to preparative thin layer chromatography (PTLC) is described. However, in the PTLC, the solid material obtained by concentrating the fraction extracted containing the object compound to solidification is in the amorphous form and is low in stability, and not high in purity. Therefore, it is not desirable for a commercial product. Accordingly, there remains a need an improved means of preparing this compound.
The problem to be solved by the present invention is to provide N-[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester as a crystal which is high in stability and also good in purity, and therefore which is desirable for making the compound a commercial product.
The present inventors have earnestly studied this problem described, and, as a result, have found a crystal of N-[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester, while the compound was heretofore only in the amorphous form, to reach to a completion of the present invention. The crystal thus found is excellent in stability and purity.
Thus, the present invention provides the following:
(1) A crystal of N-[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester.
(2) A crystal of N-[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester, which exhibits X-ray diffraction peaks at least diffraction angles of 8.2xc2x0, 14.7xc2x0, 20.5xc2x0 and 22.4xc2x0 (2xcex8, CuK xcex1 ray) when determined in the powder X-ray diffractometry, which hereinafter may be referred to as xe2x80x9cA-type crystalxe2x80x9d.
(3) A crystal of N-[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester, which exhibits X-ray diffraction peaks at least diffraction angles of 4.8xc2x0, 7.3xc2x0, 9.9xc2x0 and 20.0xc2x0 (2xcex8, CuK xcex1 ray ) when determined in the powder X-ray diffractometry, which hereinafter may be referred to as xe2x80x9cB-type crystalxe2x80x9d.
(4) A crystal of N-[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester, which exhibits X-ray diffraction peaks at least diffraction angles of 4.7xc2x0, 8.0xc2x0, 9.0xc2x0, 14.0xc2x0, 20.2xc2x0 and 24.3xc2x0(2xcex8, CuK xcex1 ray) when determined in the powder X-ray diffractometry, which hereinafter may be referred to as xe2x80x9cC-type crystalxe2x80x9d.
In the present invention, N-[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-xcex1-aspartyl]-L-phenylalanine 1-methyl ester, which is a sweetener with a high potency of sweetness, is be obtained in the crystalline form. Such a crystalline product is favorable as a commercial (industrial) product. In addition, the crystalline form of the compound has excellent stability and high purity.
Thus, the present invention also provides a method of sweetening a food or beverage product, comprising incorporating the crystal described above into a food or a beverage product.
The present invention also provides a food or beverage composition comprising a food or a beverage and the crystal described above.
A more complete appreciation of the invention and many of the attendant advantages thereof will be readily obtained as the same becomes better understood by reference to the following Figures in conjunction with the detailed description below.